文献类型：期刊文献

英文题名：Palmitate induces VSMC apoptosis via toll like receptor (TLR)4/ROS/p53 pathway

作者：Zhang, Yuanjun[1,2];Xia, Guanghao[1,3];Zhang, Yaqiong[2];Liu, Juxiang[1,3];Liu, Xiaowei[1];Li, Weihua[3];Lv, Yaya[1,3];Wei, Suhong[1,3];Liu, Jing[1,3];Quan, Jinxing[1,3]

第一作者：Zhang, Yuanjun;张亚娟;张玉洁;张亚菊

通信作者：Quan, JX[1]

机构：[1]Gansu Prov Hosp, Dept Endocrinol, Lanzhou, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Lanzhou, Peoples R China;[3]Key Lab Endocrine & Metab Dis Gansu Prov, Lanzhou, Peoples R China

第一机构：Gansu Prov Hosp, Dept Endocrinol, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Hosp, Key Lab Endocrine & Metab Dis Gansu Prov, Dept Endocrinol, Lanzhou 730000, Peoples R China.

年份：2017

卷号：263

起止页码：74

外文期刊名：ATHEROSCLEROSIS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000407634000887)】；

基金：This research was supported by grants from the National Natural Science Foundation of China (Grant number: 81260136, 30960147).

语种：英文

外文关键词：Palmitate; Vascular smooth muscle cells; Apoptosis; Oxidative stress; Toll-like receptor 4

摘要：Background and aims: Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. Methods: VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 20,7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. Results: Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. Conclusions: Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis. (C) 2017 Elsevier B.V. All rights reserved.